The young, healthy vitreous is a homogeneous, optically transparent gel filling the posterior segment of the eye. Gel vitreous volume increases during the first decade while the eye is growing in size and then remains stable until about the age of 40 years, when it begins to decrease in parallel with an increase in liquid vitreous. Macromolecular changes occurring during this process result in inhomogeneities within the vitreous. Concurrently, changes occurring at the vitreo-retinal interface allow the posterior vitreous cortex to detach from the internal ILL of the retina. When liquefaction and dehiscence occur simultaneously and in concert, the result is an innocuous posterior vitreous detachment (PVD). When the natural processes do not occur in concert, an anomalous PVD (APVD) may develop. The ability to diagnose precursors of APVD and to differentiate normal changes in vitreous related to aging from abnormal changes would permit early intervention before vitreo-retinal diseases progress to an advanced state. This would have a significant clinical impact by decreasing the likelihood of blindness, and reducing the cost of treatment and the risk to patients associated with advanced disease states. More broadly, early diagnosis has the potential to impact therapeutics of systemic diseases of the body such as diabetes.
The most clinically significant vitreo-retinal disease is diabetic retinopathy. The increased glucose levels in the vitreous of diabetic subjects have been shown to be associated with increased nonenzymatic glycation products and elevated levels of cross-linking and aggregation of vitreous collagen fibrils. Alteration of the vitreous due to poor glycemic control can extend or contract the vitreous hyaluronan, induce an APVD. and predates by years the optically visible evidence of retinal disease such as microhemorrhages, microaneurysms, leakage with hard exudates (detectable by examination and photography), and edema or neovascularization (detectable by fluorescein angiography). Unfortunately, because no current diagnostic technology is able to detect the precursors of diabetic retinopathy, the disease is typically only detected in the aforementioned advanced states at which point treatments are costly, difficult to implement, carry some risk to patient or may be too late to prevent blindness. The ability to detect and quantify the macromolecular and physiopathologic abnormalities of the vitreous much earlier in disease progression would permit better disease management, reduce ultimate treatment cost, and reduce the ultimate risk blindness.
Another vitreo-retinal disease affecting a significant number of patients is high myopia (exceeding −6 diopters), which has a 4% prevalence in the general population. Biochemical studies in myopic human eyes found a decreased collagen content and concentration in the central vitreous. The vitreous body in myopia becomes liquefied and contains filaments with localized nodules. The formation of liquid vitreous in myopia markedly destabilizes vitreous and threatens the retina because this process occurs relatively early in life and is not concurrent with dehiscence at the vitreo-retinal interface. This is different from the mechanism of vitreous liquefaction seen in aging, wherein the increase in liquid vitreous volume occurs in synchrony with decreased adhesion of vitreous to retina. The increased rate of liquefaction in high myopia leads to an increased incidence of PVD that typically occurs 5 to 10 years earlier than age-normal subjects. Myopic patients have a much greater risk of retinal detachment and, without treatment, blindness. A non-invasive diagnostic tool that does not require dilation that is capable of characterizing changes to the vitreous that signal a risk in a given individual, would permit early intervention.
Floaters are a common complaint related to myopia, PVD, and vitreous liquefaction/collagen aggregation due to aging, inflammation, and diabetes. Floaters move with vitreous displacement during ocular saccades and scatter incident light, casting a shadow on the retina that is perceived as a hair-like structure. PVD may also induce a glare caused by light scattering from condensed vitreous fibers, the detached posterior vitreous cortex, glial tissue of epipapillary origin adherent to the posterior vitreous cortex, or intravitreal blood. However, nothing is known about the size, number, or location of floaters as they relate to disease progression and normal aging.
To more effectively diagnose, treat, and ultimately prevent disorders of the vitreous, a rapid, safe, reproducible, and objective way to quantify the state of opacification (i.e., inhomogeneity) of the vitreous is needed. This approach differs from typical ophthalmic ultrasound devices that are designed to image the front or back of the eye rather than the vitreous. Because inhomogeneities within the vitreous are non-uniformly distributed, the method to quantify inhomogeneities would ideally make use of data obtained throughout the vitreous volume. Optical coherence tomography (OCT) permits visualization of abnormalities in the vicinity of the vitreo-retinal interface, but does not permit assessment of peripheral retinal pathology or imaging of the sclera and orbital tissues, nor does it allow assessment of motility of vitreous membranes in response to saccades, which is readily accomplished with real-time ultrasound. Ultrasound permits visualization of the entire vitreous and is sensitive to micro-scale (on the order of 20 μm) tissue properties related to changes in mass density and speed of sound (e.g., liquefaction vs. normal vitreous) and particle size and particle concentration (e.g., collagen aggregation, cell migration and proliferation within certain regions of the vitreous body.